During this period, the collaborative team has worked to validate and characterize hits previously identified in the primary screen, selecting specific chemotypes for medicinal chemistry optimization. Initial results of the structure activity relationship studies show considerable improvements in potency with some of the molecules. The team is also working in developing in vitro mineralization protocols using progenitor bone cells that facilitate functional characterization and rank order of improved molecules beyond signalling assays. Selected optimized compounds with reasonable metabolic stability and physico-chemical properties will be consider for pharmacokinetic studies and eventually in vivo efficacy evaluation.